Functional Characterisation Of Long Spliced NcRNAs
Funder
National Health and Medical Research Council
Funding Amount
$649,230.00
Summary
Genome sequencing projects suggest we only have approximately thirty thousand coding genes which was previously considered to be far too few to provide the blueprint for generation of human complexity. More surprising was the discovery that 3-5% of the genome is transcribed but not translated into protein. The function of these non-coding RNAs is unknown but hotly debated. Is it junk? Or does it play a new key role in programming development? This grant will address this question directly.
Role Of DNA Methylation And Non-coding RNA In Human Centromere Function
Funder
National Health and Medical Research Council
Funding Amount
$499,000.00
Summary
A chromosome is a grouping of coiled strands of DNA, containing many genes. Every human cell has 23 pairs of chromosomes, which together comprise the genome. Both gain and loss of any of these chromosomes will lead to severe medical problems including birth defects and cancer development. Thus, the understanding of the mechanisms underlying the exact passage of these chromosomes from a parental cell to two new cells during cell division, and how the information is copied from from one cell gener ....A chromosome is a grouping of coiled strands of DNA, containing many genes. Every human cell has 23 pairs of chromosomes, which together comprise the genome. Both gain and loss of any of these chromosomes will lead to severe medical problems including birth defects and cancer development. Thus, the understanding of the mechanisms underlying the exact passage of these chromosomes from a parental cell to two new cells during cell division, and how the information is copied from from one cell generation to another, is an important area of research, however, much remains to be learnt about the mechanisms. Our laboratory was the first to discover a key component of the chromosome that is involved in the regulation of the cell division process, ensuring the accurate segregation of chromosomes. This structure, known as a neocentromere, is an ideal model system to study important aspects of chromosome segregation. The present project proposes to study the properties of this neocentromere in detail. The outcome will contribute to our knowledge on the processes underlying cell and chromosome division, which will ultimately have a direct impact on our understanding of the causes for some of the most common clinical conditions that affect human health.Read moreRead less
MRNA Surveillance In Human Disease: Molecular Determinants Of Nonsense-mediated MRNA Decay
Funder
National Health and Medical Research Council
Funding Amount
$474,517.00
Summary
Inherited diseases are a common cause of human disability, illness and suffering. It has been estimated that 5-10% of the population will be affected by disorders with a genetic component. Thus studies on mechanisms of inherited diseases, especially those relating to genetic mechanisms with relevance across a wide range of individual disorders and gene mutations, are of great significance in diagnosis, molecular pathology and the eventual development of therapeutics. While there are many types o ....Inherited diseases are a common cause of human disability, illness and suffering. It has been estimated that 5-10% of the population will be affected by disorders with a genetic component. Thus studies on mechanisms of inherited diseases, especially those relating to genetic mechanisms with relevance across a wide range of individual disorders and gene mutations, are of great significance in diagnosis, molecular pathology and the eventual development of therapeutics. While there are many types of mutations, one relatively common type is called a premature termination mutation. Premature termination mutations introduce an inappropriate genetic signal that tells the cells to stop the formation of proteins before they are complete. This would result in the production of a protein that is shorter than normal, and these short proteins could be quite abnormal and drastically affect the normal function of cells. To overcome this, cells have developed elegant strategies that involve the deployment of quality control, or surveillance, mechanisms to remove the mutant gene product before it can be converted into an abnormal protein. This process is called nonsense mediated decay. Nonsense mediated decay is a complex process and some of the key components have been identified by studies on a small number of genes. However, our studies have identified several previously unknown aspects of the process that suggest that the currently held view of how nonsense mediated decay works is only the beginning of the story and further important complexity exists. The proposed research will explore the basic mechanisms of the surveillance process and determine the signals that initiate nonsense mediated decay. Since premature termination mutations cause one-third of all inherited genetic disorders, our studies will provide new insights into the surveillance mechanisms and will have wide applicability to our understanding of the basis of inherited disease.Read moreRead less